Choline alfoscerate, which is an acetylcholine precursor, supplies deficient acetylcholine to restore neurotransmission in the nervous system and repairs damaged nerve cell membranes to normalize neuronal functions. And also, choline alfoscerate normalizes acetylcholine receptor functions in the post-synaptic nerve terminal so as to facilitate neurotransmission, thereby improving the secondary symptoms caused by cerebrovascular defects and the symptoms caused by denatured or degenerative organic brain syndrome. Therefore, choline alfoscerate has been known to be useful for treating senile hypermetamorphosis such as memory impairment, mental derangement, disorientation, and attention deficiency; the change of feeling and behavior such as emotional instability and irritability; senile pseudo-depression and so on. Choline alfoscerate is commercially available in the form of soft capsule, which is orally administered at the dose of 400 mg twice or three times a day.
Meanwhile, choline alfoscerate tends to be dissolved by pulling moisture in from the surrounding air, thereby exhibiting deliquescence and/or hygroscopicity. Therefore, choline alfoscerate is commercially available in the form of soft capsule formulation, which is prepared by filling the liquid phase of choline alfoscerate in soft gelatin capsules. However, in the soft capsule form formulation, choline alfoscerate may move into soft gelatin shells over time. Microorganism deterioration also exists in the soft capsule form formulation. Further, the soft capsule formulation is weak to humidity and heat, which may cause stability problems, e.g., when stored in summer season.
In order to address the deliquescence of choline alfoscerate and the disadvantages of the soft capsule formulation, various researches have been carried out for developing formulations having solid dosage form. For example, Korean Patent Publication No. 10-2009-0088564 discloses a choline alfoscerate-containing pharmaceutical preparation in which choline alfoscerate is adsorbed on colloidal silicone dioxide. Korean Patent No. 10-1172699 discloses a pharmaceutical formulation comprising an adsorption product obtained by adsorbing the choline alfoscerate on magnesium silicate aluminate in a weight ratio of 1:1 to 2:1. And also, Korean Patent No. 10-1257919 discloses a pharmaceutical composition comprising coated particles obtained by coating choline alfoscerate particles with a water soluble polymer such as hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinyl alcohol, methacrylic acid copolymers, polyethylene oxide and so on.
However, the prior art formulations require adsorbing the drug itself (i.e., choline alfoscerate) to an excipient (Korean Patent Publication No. 10-2009-0088564, Korean Patent No. 10-1172699) or performing particle-coating processes (Korean Patent No. 10-1257919). In other words, since the prior art formulations require performing adsorption processes or particle-coating processes, the processes for preparing the formulations are complicated and specific equipment (e.g., fluidized bed granulator and so on) is also required. Therefore, the costs for the process are very high and it is difficult to apply to industrial mass production. Furthermore, if a tablet is prepared by using choline alfoscerate adsorbed on colloidal silicon dioxide according to Korean Publication No. 10-2009-0088564, the size of the resulting tablet becomes too large, which results in problem of decreasing patient compliance.
Hence, there is a need to develop a choline alfoscerate-containing tablet which can be prepared according to conventional methods for preparing a tablet without performing additive-adsorption and/or particle-coating. And also, there is a need to develop a choline alfoscerate-containing tablet which can prevent deliquescence and hygroscopicity of choline alfoscerate and exhibit equivalent dissolution pattern to the commercially available soft capsule formulation.